Open Access Research

ATP synthase ecto-α-subunit: a novel therapeutic target for breast cancer

Jian Pan12, Li-Chao Sun2, Yan-Fang Tao1, Zhuan Zhou23, Xiao-Li Du24, Liang Peng25, Xing Feng1, Jian Wang1, Yi-Ping Li1, Ling Liu1, Shui-Yan Wu1, Yan-Lan Zhang1, Shao-Yan Hu1, Wen-Li Zhao1, Xue-Ming Zhu1, Guo-Liang Lou16* and Jian Ni7*

Author Affiliations

1 Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, 215003, China

2 State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China

3 Hillman Cancer Center Lab, Department of Pathology, Pittsburgh University, G21 5117 Center Ave. Pittsburgh, PA 15206, USA

4 Laboratory of Cellular Oncology, National Cancer Institute, NIH, Building 37, Room 4112, Bethesda, MD 20892, USA

5 Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, China

6 Translational Research Center, Chang Hai Hospital, the Second Military Medical University, Shanghai, China

7 Translational Research Center, Second Hospital, The Second Clinical School, Nanjing Medical University, Nanjing, China

For all author emails, please log on.

Journal of Translational Medicine 2011, 9:211  doi:10.1186/1479-5876-9-211

Published: 8 December 2011

Abstract

Background

Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.

Methods

Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).

Results

Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.

Conclusions

Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

Keywords:
Two-dimensional liquid phase chromatographic fractionation; ATP synthase α-subunit; Tissue microarray; breast cancer; monoclonal antibody